Resolution of heterocyclic nitro



Patented July 16, 1946 RESOLUTION OF HETEROCYCLIC NlTRO- GEN COMPOUND MIXTURES Karl Henry E'rigel, Teaneck, N. J assignor to Allied Chemical & Dye Corporation, New York, N. Y., a corporation of New York NoDrawing. Application March 10, 1943, Serial No. 478,637

Claims. (Cl. 260-290) This invention relates to the resolution of mixtures of heterocyclic nitrogen compounds containing pyridine homologs such as 3-picoline, 4-picoline and 2,6-lutidine.

- The piccl-ines, other homologs of pyridine, and pyrrole are customarily extracted, along with pyridine, from coal tar oils and other sources of these heterocyclic nitrogen compounds by means of an aqueous solution of mineral acids, usually sulfuric acid, and are liberated from the acid solutions by the addition of alkali hydroxide or carbonates. Mixtures of nitrogen compounds thus liberated are then fractionally distilled. Bases such as pyridine, boiling point 116 0., and 2-picoline, boiling point l29.4 C., can generally be obtained in reasonably pure form by fractional distillation, but for the most part the remaining compounds cannot be separated by distillation methods alone. Instead, the fractions obtained, even when they are of relatively narrow boiling range, contain increasing numbers of pyridine homologs or their isomers. Mixtures of this kind have found limited practical application mainly as special solvents and are of relatively low economic value. The individual compounds, however, if they could be readily isolated would be of far greater value, for example, in the preparation of derivatives, especially pharmaceutical products and dyes. The requirements for purity in these fields are extremely severe.

Of especially high potential value are the nitrogen compounds in the fractions having a boiling range of about l40-148 C. A typical mixture recovered from most types of coal tar, for

example, is the fraction boilingin the vicinity of 143-145 C. containing as predominant components three pyridine homologs of substantially the same boiling point in roughly equal proportions; i. e., 2,6-lutidine, boiling point 143.8 0., E-picoline (beta-picoline) boiling point 143.8 C.,

and 4-pico1ine (gamma-picoline), boiling point,

2 I chemicals. Nicotinic acid, for example, a member of the vitamin B complex, may be readily obtained by oxidation of '3-picoline.

Since the three components making up the usual nitrogen base fractions boiling in the range 140-l48 C. (2,6-lutidine, 3-picoline', and 4-picoline) have substantially the same boiling points, and since pyrrole, present in some of these fractions, forms azeotropes with these bases, fractional distillation is obviously unsatisfactory as a means for resolving the mixtures. Other methods of resolving such mixtures heretofore described in the published prior art have been generally unsatisfactory in regard to products, yields, and production costs. Such other methods have usually depended upon fractional crys tallization of the more common salts of the bases present, e. g., the chlorides, sulfates, oxalates, chlorates, picrates, ferrocyanides, and the like. Isolation or purification of individual bases by such methods has been found to be extremely cumbersome and generally insuficiently sharp to obtain compounds of a purity demanded in industry. These methods also have often presented other drawbacks such as prohibitive cost, explosive hazards, and toxicity.

It is an object of this invention to provide a commercially attractive process of obtaining pure or enriched 4-picoline and 3-picoline from mixtures of these compounds and other heterocyolic' nitrogen compounds not readily separable therefrom by distillation.

It is a further object of this'invention to providea' commercially feasible process for resolving the usual fractions of heterocyclic nitrogen compounds, particularly tar-basefractions boiling in the range l40-l48 C;, which fractions generally contain 2,6-lutidine,3-picoline and 4- picoline in substantial proportions, and may contain pyrrole.-

I have discovered, that mixtures containing 3- picoline, 4-picoline, and 2,6-lutidine may be resolved into separate fractions, each enriched in one of these bases, by subjecting to dry distillation, preferably under reduced pressure, a calcium chloride addition product of such base mixtures. I have found there are sharp: differences in decomposition vapor pressures between'the calcium chloride addition compounds of the three pyridine homologs, 2,6-lutidine compounds having by far the highest vapor tension, S-picoline compounds a lower one, and 4-picoline compoundsv the lowest. Thus, it is possible, to obtain as a first distillate from a calciumchloride addition product of a 2,6-lutidine-3-picoline-4-picor 3 line mixture a 2,6-lutidine concentrate containing generally about 87% 2,6-lutidine with 3-picoline and. very little ii-picoline present. -A further dis: tillate consists of a 3-picoline concentrate containing about 72% 3-picoline and 28% 4-pic0- line. 'The final distillate consists of a 4-picoline concentrate containing generally about 92% 4- picoline, with 8% 3-picoline present. This is particularly surprising since 3- and l-picolines individual bases, as above described, from base mixtures containing any two of the bases 3: picoline, it-picoline and; 2,6-lutidine. Thus, a 3- and ii-picoline mixture may be resolved into a 3-pico1ine concentrate and a e-picoline con centrate; similarly, a mixture of 2,6-lutidine withreither 3- or l-picoline may be resolved into a 2,6-lutidine concentrate and a 3-picoline or Jr-picoline concentrate.

The bases 3-picoline, ll-picoline and 2,6- lutidine .arepresent generally in the heterocyclic nitrogen, compound mixtures separated from materials such as coke-oven distillates, cracked petroleum, shale tar, bone oils and other natural, as well as synthetic, nitrogenous materials. As above pointed out, when two or more of the bases S-picoline, -picoline and 2 ,6-lutidine are present in such mixtures, ordinary fractional distillation is. not effective to isolate these bases from'eachother. ,Instead, upon fractional distillation, these three pyridine homologs, differing by not more thana degree centigrade in their boiling ,points, become concentrated in fractions boiling in the range PLO-148 C. For example, the beta-gamma picoline fraction recovered from pyrrole-free coal tar generally boils in the range 140-145 C. and has the following approximate composition:

. V V Per cent 2,6-lutidine 20-45 3 -picoline 30-35 4-picoline 30-40 In addition, this fraction may contain a small percentage of 2-picolin'e and 2,4-lutidine, When pyrrole is present, a close-cut fraction contain- .ing these bases and pyrrole generally boils in the range 145148 C.

A fraction to which the process ofmy invention is applicable may thus be obtained from-a heterocyclic nitrogen compound mixture that contains two or more ofthe pyridine homologs this close-cut fraction to their calcium chloride addition compounds, and subjecting-to dry dis tillatipnto obtain individual base concentrates,

as; above described. In some of the claims I have indicated the dry distillation is to be ap- .plied toa calcium chloride addition-product of a mixture of pyridine homologs boiling in the range 140-l48 C. this expression is intended. oyd e teis p x i r r wh ch, c nta ns a l a 45 taina desired constantpressure.

4 two of the pyridine homologs 3-picoline, 4- picoline and 2,6-lutidine in substantial proportions, and. generally contains all three of these As above pointed out, such a mixture may also contain pyrrole, and may contain small bases.

amounts of bases boiling outside the range 140-148 C., e. g., bases such as Z-picoline and 2,4-lutidine.

:My invention further comprises a process in 10 which the above-described dry distillation of calcium chloride addition compound is combined with additional treatments, as described below, for isolating substantially pure bases from the various base concentrates obtained by the dry distillation of the calcium chloride ad-- dition compounds. V

In a preferred method of practicing my in- 'vention, a pyridine homolog fraction, as above described, boiling in the range 140-148 C'. is

converted into a mixture of calcium chloride addition compounds, preferably by adding the base mixture gradually to a charge of anhydrous calcium chloride. The proportion of calcium chloride to crude basesin' this charge is preferably. approximately in a molar ratio of 1 to 2.

with the 3- and 4-picolines present in a ratio of one mol of calcium chloride to two of base.

Excess calcium chloride over that required to combine with all bases present is not harmful.

The dry-distillation operation resembles in principle the drying of a solid at successive temperature levels and accordingly I have found it advantageous to carry out the distillation in an apparatus of a type often employed as a drier for solids, consisting of a rotary iron vessel pro- 49 vided with a slowly revolving agitator, a trap to retain dust, a vapor outlet connecting with a condenser cooled with a circulating water, and receivers. The drier-condenser system is preferablyconnected to a vacuum pump to main- Vapor losses through the exhaust of the pump may be avoided by passing such vapors through suitable scrubbers which retain bases, preferably through scrubbers containing solutions of mineral acids.

may be jacketed for heating with a fluid heating medium.

lar-operation, the greater part of the calcium chloriderequired'for a charge will be the residual calcium chloride left in the drier at the conclusion of the dry distillation of a previous batch,'sinc e this calcium chloride is in the desired powdered anhydrous form. Small mechanicallosses of calcium chloride, such as loss throughdust traps, maybe made up, between successive charges, by addition of a technical grade ofcalcium chloride (78% to 80%). Mois- 565 .ture which such material contains is distilled,

as -ajpreliminary fraction, before taking off the desired base distillate fractions.

.' As abovestated, the base mixture is slowly added .to a charge of calcium chloride. A small amount of calcium chloride-lutidine-picolines tion. This, isrdcsirable inorder to make certain The 50 drier may be fired directly, e. g., with gas, or

that-combination of base withcalcium chloride occurs about as rapidly as the base is added, since accumulations of unreacted free base may lead to final rapid reaction and formation of large solid aggregates which makes further. agitation difficult. i

The charge is agitated, and uniformly and gradually heated, preferably under a reduced pressure varying from about to about 100 mm. mercury. Vapors consisting of free bases are carefully condensed in a series of receivers. The first nitrogen base distillate fractiontaken consists of a 2,6-lutidine concentrate which under equilibrium conditions contains about 87% of 2,6- lutidinewhen the starting material is a base mixture that contains no substantial amount of material other than 2,6-lutidine, 3-picoline and 4- picoline. The 2,6-lutidineconcentrate thus obtained contains also about 9% 3-picoline and about 4% 4-picoline. When pyrrole is present in the original base mixture, it will come over with the 2,6-lutidine concentrate and the proportion of 2,6-lutidine will be accordingly decreased. This lutidin concentrate continues to come over until more than 95% of the 2,6-lutidine has been removed from the mixture in the still.

When about 4% of the 2,6-lutidine still remains in the material in the still, the distillation temperature rises and at a higher temperature level a small quantity of an intermediate fraction (generally about one-tenth of the volume of the principal fractions) distils over until the 2,6-lutidine has been completely removed; this fraction under equilibrium conditions contains about 35% 2,6- lutidine, about 45% 3'-picoline, and about 20% 4- picoline. This small quantity of mixed base is returned to the process, i; e., 'isadded to the next batch.

The temperature of distillation rises again and at a higher temperature level a 3-picoline concentrate is taken on as distillate. This concentrate under equilibrium conditions contains about 72% 3-picoline and about 28% 4-picoline.

The base component of the material remaining in the still at this point contains about 92% 4-picoline and about 8% 3-picoline. This 4- picoline concentrate may be distilled off at a still higher temperature or may be recovered by addition of water to the still residue, thus decomposing the calcium chloride addition compounds. 4-picoline is then obtained by steam distillation or partial evaporation of the mixture. It is preferable to remove the 4-picoline concentrate by dry distillation, since this leaves powdered anhydrous calcium chloride ready to be reused for forming the calcium chloride addition product of the next batch of base mixture. When water has been added to the still residue and the 4-picoline concentrate removed by steam distillation, in order to reuse the calcium chloride it is necessary to evaporate the residual solution to dryness and to grind the solid calcium chloride thus obtained.

As above stated, a reduced pressure of about 5 to 100 mm. mercury is preferably employed during the dry distillation. At a pressure of 5 mm. mercury, the 2,6-lutidine concentrate distils ofi in the neighborhood of 15 C., the 3-picoline concentrate in the neighborhood of 70 C., and the 4-picoline concentrate in the neighborhood of 175 C. In actual operation, the fractions would generally'be taken through a range extending from 10 to 20 below and above these temperatures. At a pressure of 100 mm. the 2,6-lutidine concentrate comes off in the neighborhood of'80" C., the 3 pi'coline concentrate in the neighborhood of -140.6 to l44.4 C., corrected temperatures.

6 185 C., and the 4-picoline concentrate in the neighborhood of 275 C. In this case also, the distillate fractions would be taken through a range extending considerably below and. above these temperatures. Pressures lower than 5 mm. and higher than mm. may-be employed. In general, I have found that low pressures (and correspondingly low temperatures) permit the sharpest separation. However, the use of pros sures lower than about 5 mm. requires the use of lower condenser temperatures, even brine cooling in some instances, to condense thefree base i that distils off, whereas the use of pressures'higher than about 100 may require temperatures of 300 C. or higherto decompose the most stable of the addition products, namely the addition product of the 4-picoline concentrate.

I have found that 40-60 mm. represents the up to a temperature of about 215 C.; and the last fraction, the 4'-picoline concentrate, is taken from that point up to a temperature. of about 280 C.

The products obtained by the process of my invention are dry, water-white products which find a ready market without further treatment. The 3-picoline concentrate, e. g., containing 72% of 3-picoline, may be used directly for production of nicotinic acid by oxidation. When substantially pure bases are desired, these may be prepared from the various base concentrates by=methods isclosed in copending applications. Pure 2,6- lutidine may be prepared from 2,6-lutidine, concentrate, for example, by precipitation as phosphate, in accordance with my copending application Serial No. 346,347, filed July 19, 1940. When pyrrole is present in the first distillate fraction, this may be removed by the process of one of my copending applications, Serial No. 463,736, filed October 29, 1942, or Serial No. 487,975, filed May 21, 1943. Pure 3-picoline may be prepared from the 3-pico1ine concentrate by precipitation as phosphate, in accordance with the process of my copending application Serial No. 346,347, referred to above, or by distillation in the form of its hydrochloride, in accordance with the process of copending application Serial No. 452,369, filed .July 25, 1942. Pure 4-picoline may be obtained, if desired, from the 4-picoline concentrate by crystallizing the calcium chloride addition compound of this base, in accordance with the process of copending application Serial No. 441,557,filed May 2, 1942,

The following. example is illustrative of the process of my invention:

The mixture of heterocyclic bases used in this example had a boiling range (bulb distillation) of specific gravity at 20 C. was 0.943. The material had approximately the following composition:

4-picoline -l -1 32 the remainder consisting of 2-picoline and 2,4-

lutidin; 1Q r The apparatus consisted of a gas-heated stationary drier of iron constrution, provided with a slowly revolving agitator, a trap to retain--dusted in'o aterials, a condenser cooled with circulating water at about 5-10 C., and receivers. was connected to a vacuum pump to maintain a desired constant pressure. The drier was charged with 600 parts by weight, of powdered anhydrous calcium chloride. A supply of calcium chloride- The drier lutidineepicolines additioncompound saved from a preceding operation, and sufficient for proper inoculation, was dispersed throughout the powdered calcium chloride to initiate prompt crystallization. A mixture of bases was gradually added to the the calcium chloride at atmospheric pressure, making certain that combination occurred about as rapidly as the addition proceeded,

and that the complete addition compounds were dispersed throughout the mixture.

The combination of the materials resulted in a. V Per cent 2,6-lutidine 8'7 3-piooline i 9 a The remaining 4% consisted mainly of Z-picoline with possible traces of 4-picoline.

Receivers were changed at this point. Distillation was continued, removing a small intermediate fraction, 3.5% of original bases, while the drier temperature rose to 130 C.

' The'intermediate fraction'had the following composition:

Per cent 2,6-lutidine 35 B-picoline V 45 4-pico1ine 20 Distillation was continued until the drier tem-.

perature rose to 215 C., 39.0% of the original mixture of bases being collected in the receiver. The material had the following composition:

Per cent 3-picoline 72 l-picoline 28- After changing receivers, distillation was completed by raising the temperature inside of the drier gradually to 280 C. The material collected in this fraction represented 19% of the original mixture of bases and had the following composition: a

Per cent 3-pico1ine 8 4-picoline 92 The small intermediate fraction representing 3.5% of the total bases, was returned to a subsequent batch to be re-worked. The calcium chloride remaining as a, residue consisted of a fine char ed, U der condition e yes n' t s e *15 '8 ample, losses amounted toi {of total bases chargedf Sincecertain changes may be made in carrying out the above process withoutdeparting from the scope of the invention, it is intended that all mat: ter contained in the above description shall be interpreted as illustrative and not in a limitin sense. V

I claim: r

1. In a process'for separating components of a mixture of pyridine homologs boiling in the range 140-148 C., the steps which comprise subjecting to dry distillation a calcium chloride addition product of such'miXture, and recovering at least onedistillate fraction enriched in one of said pyridine homologs.

2. In a process for separating components of a mixture of pyridine homologs boiling in the range,

l40-14 8 C., the steps which comprise subjecting to dry distillation a calcium chloride addition product of such mixture, and recovering distillate fractions each enriched in one ofsaid pyridine homologs.

3. In a process for separating components of a mixture containing substantial proportions of pyridine homologs boiling in the range l40-148 C., the steps which comprise subjecting to dry distillation, under a pressure in the range of about 5 mm. to about mm. mercury, a calcium chloride addition product of such mixture, and

recovering at least one distillate fraction enriched in one of said pyridine homologs.

4. In a process for recovering a 2,6-lutidine concentrate from a mixture containing this base and other nitrogen bases not readily separable therefrom by distillation, thesteps which comprise forming a calcium chloride addition prodnot of said mixture, carrying out a dry fractional distillation of said product and collecting a distillate fraction enriched in 2,6-lutidine.

5. In a process for recovering a 3-picoline concentrate from a mixture containing this base and other nitrogen bases not readily separable therefrom by distillation, the steps which comprise forming a calcium chloride addition product of said mixture, carrying out a dry fractional distillation of said product and collecting a distillate fraction enriched in 3-picoline. I

6. In a process for recovering a 4-picoline concentrate from a mixture containing this base and other nitrogen bases not readily separable therefrom by distillation, the steps which comprise forming a calcium chloride addition product of said mixture, carrying out a dry fractional distillation of said product and collecting a fraction enriched in 4-picoline.

'7. A process for resolving a mixture of 2,6- lutidine, 3-picoline and 4-picoline into a 2,6- lutidine concentrate. a 3-picoline concentrate, and a 4-pic01ine concentrate, which comprises treating the mixture with an amount of calcium chloride at least sufficient to react with the picclines, subjecting this calcium chloride addition product to dry fractional distillation, under a pressure of about ,5 mm. to about 100 mm. mercury, and collecting successively a 2,6-lutidine concentrate, a 3-picoline-concentrate, and a 4- picoline concentrate. I

8. A process for recovering a 2,6-lutidine concentrate, a S-picoline concentrate, and a 4-picoline concentrate from a mixture of coal tar bases containing 2,6-lutidine, 3-picoline and l-picopicolines, subjecting this calcium'chloride addition product to dry fractional distillation under reduced pressure and collecting successively a 2,6-lutidine concentrate, a 3-pic01ine concentrate, and a -picoline concentrate.

9. In a process for separating components of a mixture of pyridine homologs boiling within the range 140148 C., the steps which com prise treating the mixture with calcium chloride, then dry distilling the resultant reaction product and collecting as distillate at least one fraction enriched in one of said pyridine homologs.

10. In aprocess for resolving a mixture of 2,6- lutidine, 3-picoline and 4-picoline, the steps which comprise treating the mixture with an amount of calcium chloride at least suflicient to react with the picolines, thereafter dry distilling the resultant reaction product and separately collecting three fractions having respectively a relatively 

